title: Effect of metformin on prostate cancer outcomes after radical prostatectomy.
abstract: OBJECTIVE
  Recent studies have shown a relative risk reduction in the incidence of prostate cancer in patients taking metformin. However, there are conflicting findings on the effect of metformin on established cases of prostate cancer. In this study we evaluated the effect of metformin on survival and pathologic outcomes in established prostate cancer.
  
  
  METHODS
  We retrospectively identified 12,052 patients who underwent radical prostatectomy between 1997 and 2010 at Mayo Clinic. Among these, 885 (7.3%) were diabetics, including 323 taking and 562 not taking metformin. Kaplan-Meier method was utilized to calculate rates of biochemical recurrence (BCR), systemic progression (SP), and all-cause mortality (ACM). Cox models were used to estimate the metformin hazard ratio (HR) adjusted for clinical and pathologic variables.
  
  
  CONCLUSIONS
  Median follow-up was 5.1 years. In univariate analysis, metformin HR (95% confidence intervals) was not significant for BCR (1.13 [0.84, 1.52]; P = 0.40), SP (1.37 [0.69, 2.72]; P = 0.37), and ACM (1.32 [0.84, 2.05]; P = 0.23). After adjusting for covariates of interest, the HRs for metformin among diabetics remained nonsignificant for BCR (0.91 [0.67, 1.24]; P = 0.55), SP (0.83 [0.39, 1.74]; P = 0.62); and ACM (1.16 [0.73, 1.86]; P = 0.53). No significant difference was seen between metformin users and nonusers in the final pathologic Gleason score (P = 0.33), stage (P = 0.1), rate of positive surgical margins (P = 0.29), or tumor volume (P = 0.76). Metformin use was not associated with a risk reduction in BCR, SP, or ACM. Besides presenting survival data, our results describing metformin's effect on final pathology are unique.
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Dharam
authors.initials: D
authors.lastname: Kaushik
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN. Electronic address: karnes.r@mayo.edu.
authors.forename: R Jeffrey
authors.initials: RJ
authors.lastname: Karnes
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Manuel S
authors.initials: MS
authors.lastname: Eisenberg
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
authors.forename: Laureano J
authors.initials: LJ
authors.lastname: Rangel
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Carlson
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Bergstralh
mesh_terms: D000368:Aged; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000601:surgery*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Biochemical recurrence; Disease progression; Metformin; Prostate cancer; Prostatectomy; Survival rate